Download Gene therapy and Viral Vector

Human Health and Disease
Lecture 7
Cancer Therapy
Surgery: Removal of cancerous
tissue/cyst/organ
 Radiation Therapy: Use of high doze of
radiation to kill cancer cells and shrink
tumors
 Chemotherapy: Use of drugs to induce
apoptosis in cancerous cells.
 Immunotherapy: Helps immune system to
fight cancer.
 Hormone therapy: Slows or stops the
growth of cancerous cells that use
hormones to grow.
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Cancer therapy
Stem cell transplant: Procedures that
restore blood-forming stem cells in
people who have their destroyed by high
doses of cancer treatments, such as
chemotherapy and radiation therapy.
 Gene Therapy: Use of viral and non-viral
vector to replace mutated genes.
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Cancer Biopsy
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An incisional biopsy is the removal of a piece
of the suspicious area for examination.
An excisional biopsy is the removal of the
entire suspicious area, such as an unusual
mole or a lump.
After a biopsy, the tissue removed is
examined under a microscope by a
pathologist. The pathologist provides
a pathology report to the surgeon or
oncologist, who makes the diagnosis of the
type and stage of cancer.
Cancer Surgery
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Tumor removal, also called curative or
primary surgery.
The tissue surrounding the tumor is called the
margin.
Tumor removal may be the only treatment, or it
may be combined with chemotherapy, radiation
therapy or other treatments, which may be given
before or after surgery.
Conventional surgery requires large cuts, called
incisions, through skin, muscle, and sometimes
bone.
However, in some situations, surgeons can use
surgical techniques that are less invasive, which
may speed recovery and reduce pain afterwards.
Cancer Surgery
Debulking. When the complete removal
of a tumor is not possible or might cause
excessive damage to the body, surgery is
used to remove as much of the tumor as
possible.
 Other treatments, such as radiation
therapy or chemotherapy, may sometimes
also be used to shrink the remaining
cancer.
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Cancer Surgery
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Palliation. Palliative surgery is used to relieve side effects caused by a tumor.
It plays an important role in improving quality of life for patients with
advanced cancer or widespread disease. Examples include the following:
Surgery may be used to help relieve pain or restore physical function if a
tumor presses on a nerve or the spinal cord, blocks the bowel or intestines,
or creates pressure or blockage elsewhere in the body.
Surgery may be used to help stop bleeding. Certain cancers are more likely to
cause bleeding because they occur in areas with a high concentration of
blood vessels, such as the uterus, or organs in which the tumors are fragile
and can easily bleed when food and waste products pass through, such as the
esophagus, stomach, and bowel. In addition, bleeding may be a side effect of
some drugs used to treat cancer. When surgery is needed to stop bleeding, a
common technique is suture ligation, which involves tying blood vessels using
surgical thread.
Surgery may be used to insert a feeding tube or tubes that deliver
medications. If the cancer or cancer treatment has made it difficult to eat, a
feeding tube may be inserted directly into the stomach or intestine through
the abdominal wall. Or a tube may be inserted into a vein to deliver pain
medication or chemotherapy.
Surgery may be used to prevent broken bones. Bones weakened by cancer or
cancer treatment can break easily and often heal slowly. Inserting a metal rod
may help prevent fractures of weak bones and relieve pain during healing.
Cancer Surgery
Reconstruction. After primary cancer surgery,
surgery may be an option to restore the body's
appearance or function. This is called
reconstructive or plastic surgery.
 Reconstructive surgery may be done at the same
time as surgery to remove the tumor.
 Or, it may be done later after a person has healed
or received additional treatment.
 Examples of reconstructive surgery include breast
reconstruction after a mastectomy and surgery to
restore a person’s appearance and function after
surgery to the head and neck area.
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Cancer Surgery
Prevention. Some surgery is performed to
reduce the risk of developing cancer.
 For example, doctors often recommend the
removal of precancerous polyps in the colon to
prevent colon cancer.
 In addition, women with a strong family history of
breast or ovarian cancers or known mutations to
the BRCA1 and BRCA2 breast and ovarian cancer
genes may decide to have a mastectomy, which is
the removal of the breast, or an oophorectomy,
which is the removal of the ovaries, to lower the
risk of developing breast or ovarian cancer in the
future.
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Chemotherapy
Side effects of Chemotherapy
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Fatigue
Headaches
Muscle pain
Stomach pain
Pain from nerve damage, such as burning,
numbness, or shooting pains, usually in the fingers
and toes
Mouth and throat sores
Diarrhea
Nausea and vomiting
Constipation
Blood disorders
Side effects of Chemotherapy
Nervous system effects.
Some drugs cause nerve damage. This can cause the following nerve
or muscle symptoms:
 Tingling
 Burning
 Weakness or numbness in the hands, feet, or both
 Weak, sore, tired, or achy muscles
 Loss of balance
 Shaking or trembling
 Stiff neck, headache, or problems seeing, hearing, or walking
normally. These symptoms usually get better with a lower
chemotherapy dose or after treatment.
Changes in thinking and memory. Some people have trouble
thinking clearly and concentrating after chemotherapy. Cancer
survivors often call this chemo brain.Your doctor might call it
cognitive changes or cognitive dysfunction.
Why does chemotherapy cause side effects?
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Chemotherapy works on active cells.
Active cells are cells that are growing and
dividing into more of the same type of
cell. Cancer cells are active, but so are
some healthy cells. These include cells in
your blood, mouth, digestive system, and
hair follicles. Side effects happen when
chemotherapy damages these healthy
cells.
What is a liposome?
◦ Spherical vesicles with a phospholipid bilayer
Hydrophilic
Hydrophobic
Uses of Liposomes
Chelation therapy for treatment of heavy
metal poisoning
Diagnostic imaging of tumors
Study of membranes
Enzyme replacement therapy
Drug/Gene Delivery
Liposome with DNA or Drug
Entry into the cell
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A liposome has an aqueous solution core surrounded by
a hydrophobic membrane, in the form of a lipid bilayer.
Hydrophilic solutes dissolved in the core cannot readily pass
through the bilayer.
Hydrophobic chemicals associate with the bilayer.
A liposome can be hence loaded with hydrophobic and/or
and hydrophilic molecules.
To deliver the molecules to a site of action, the lipid bilayer
can fuse with the cell membrane, thus delivering the
liposome contents.
Thus preparation of liposomes in a solution
of DNA or drugs (which would normally be unable
to diffuse through the membrane) they can be
(indiscriminately) delivered past the lipid bilayer.
Entry into the cell
Nano-liposomes
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Composition: Nano-Liposomes are made up of lipids, most
of which occur naturally within the body.
Size and stability: Typically 60-80 nanometers,NanoLiposomes are stable in blood, circulate well, and easily enter
tumor cells to deliver their payloads, destroying cancer cells.
Active ingredients: both water-loving (hydrophilic) and
water-hating (hydrophobic) compounds can be loaded into
NanoLiposomes.
Protection: Actives are stored either within the liposomal
core or lipid bilayer, preventing degradation during
circulation.
Delivery: NanoLiposomes are stable during circulation and
release payloads intracellularly following membrane fusion.
Targeting: NanoLiposomes can be targeted through size
and surface charge, or a wide range of targeting materials can
be attached to the surface.
Cationic Liposome
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Cationic liposomes are structures that
are made of positively charged lipids and are
increasingly being researched for use in gene
therapy due to their favourable interactions
with negatively charged DNA and cell
membranes. They can be administered
efficiently, safely, and repeatedly for direct
gene transfer for the treatment of human
diseases. An ideal cationic liposome is
capable of targeting tumor vessels and
tumor cells.
Current liposomal drug
preparations
Type of Agents
Examples
Duanorubicin,
Doxorubicin*, Epirubicin
Anticancer Drugs
Methotrexate, Cisplatin*, Cytarabin
Anti bacterial
Triclosan, Clindamycin hydrochloride,
Ampicillin, peperacillin, rifamicin
Antiviral
DNA material
AZT
Enzymes
cDNA - CFTR*
Radionuclide
Fungicides
Vaccines
Hexosaminidase A
Glucocerebrosidase, Peroxidase
In-111*, Tc-99m
Amphotericin B*
Malaria merozoite, Malaria sporozoite
Hepatitis B antigen, Rabies virus glycoprotein
*Currently in Clinical Trials or Approved for Clinical Use
Doxil
Chemotherapy drug doxorubin
Anemia, damage to veins and tissue at injection, decrease
platelet and WBC count, toxic to the body
Treats cancer tumors
Modifications of liposome “stealth”
keeps doxorubin in blood for 50 hours instead of
20 minutes
concentrates at KS lesions and tumors
*approved by FDA in 2000*
Problems with Liposomal
Preparations of Drugs
Price
Fungizone $40.58
Amphotec $2334
Doxil $1200 per treatment, twice the cost of normal protocol
of chemotherapy and drugs
Lack long term stability (short shelf life)
Physical and chemical instability
Freeze dry and pH adjustment
Low “Pay Load” - poor encapsulation
Polar drugs and drugs without opposite charge